TY - JOUR
T1 - Altered nuclear architecture in blood cells from Huntington's disease patients
AU - de Castro, Inês J
AU - Toner, Brian
AU - Xie, Sheila Q
AU - Swingland, James
AU - Hodges, Angela
AU - Tabrizi, Sarah J
AU - Turkheimer, Federico
AU - Pombo, Ana
AU - Khalil, André
N1 - Funding Information:
We thank Aakta Patel (UCL National Hospital for Neurology and Neurosurgery) and Edward Wild (UCL National Hospital for Neurology and Neurosurgery) for collecting the blood samples; Carmelo Ferrai, former member of the Pombo lab, for the scientific advice; and the Pombo lab and the CompuMAINE lab for the helpful discussions.
Funding Information:
IJdC was supported through a PhD Studentship from FCT (BD / 43516 / 2008). AP thanks the Medical Research Council (UK) and the Helmholtz Association (Germany).
Publisher Copyright:
© 2021, Fondazione Società Italiana di Neurologia.
PY - 2022/1
Y1 - 2022/1
N2 - BACKGROUND: Cell nuclear architecture has been explored in cancer and laminopathies but not in neurodegenerative disorders. Huntington's disease (HD) is a neurodegenerative disorder that leads to neuronal death. Chromosome-wide changes in gene expression have been reported in HD, not only in the brain but also in peripheral blood cells, but whether this translates into nuclear and chromosome architecture alterations has not yet been studied.METHODS: We investigate nuclear structure and chromosome organization in HD blood cells using fluorescence in situ hybridization in ultrathin cryosections (cryoFISH), coupled with machine learning image analysis to evaluate size, distribution, and morphology of nuclei and chromosomes. Four chromosomes were analyzed based on up- or downregulation of gene expression in HD.RESULTS: We show that blood cells from HD patients display increased nuclear size and filamentary shape, increased size of gene-rich chromosome 19, decreased filamentary shape of gene-rich chromosome 22, and a more radially centralized position for chromosome 19, whereas chromosomes 4 and 5 do not show detectable differences.CONCLUSIONS: We identify gross changes in nuclear architecture and chromosome organization associated with HD in blood. This adds a new layer of information onto disrupting mechanisms in HD and increases the potential of using blood to survey HD.
AB - BACKGROUND: Cell nuclear architecture has been explored in cancer and laminopathies but not in neurodegenerative disorders. Huntington's disease (HD) is a neurodegenerative disorder that leads to neuronal death. Chromosome-wide changes in gene expression have been reported in HD, not only in the brain but also in peripheral blood cells, but whether this translates into nuclear and chromosome architecture alterations has not yet been studied.METHODS: We investigate nuclear structure and chromosome organization in HD blood cells using fluorescence in situ hybridization in ultrathin cryosections (cryoFISH), coupled with machine learning image analysis to evaluate size, distribution, and morphology of nuclei and chromosomes. Four chromosomes were analyzed based on up- or downregulation of gene expression in HD.RESULTS: We show that blood cells from HD patients display increased nuclear size and filamentary shape, increased size of gene-rich chromosome 19, decreased filamentary shape of gene-rich chromosome 22, and a more radially centralized position for chromosome 19, whereas chromosomes 4 and 5 do not show detectable differences.CONCLUSIONS: We identify gross changes in nuclear architecture and chromosome organization associated with HD in blood. This adds a new layer of information onto disrupting mechanisms in HD and increases the potential of using blood to survey HD.
UR - http://www.scopus.com/inward/record.url?scp=85105848148&partnerID=8YFLogxK
U2 - 10.1007/s10072-021-05289-w
DO - 10.1007/s10072-021-05289-w
M3 - Article
C2 - 33974169
SN - 1590-1874
VL - 43
SP - 379
EP - 385
JO - NEUROLOGICAL SCIENCES
JF - NEUROLOGICAL SCIENCES
IS - 1
ER -